Methylenecyclopropanes reactions

Due to the electronic nature of the exocyclic double bond in electron donor substituted methylenecyclopropanes, reactions can occur at the cyclopropyl carbon by attack of an electrophilic species. If both carbons of the double bond are involved, this type of reaction is referred to as a cycloaddition. 

Cycloaddition of COj with the dimethyl-substituted methylenecyclopropane 75 proceeds smoothly above 100 °C under pressure, yielding the five-membered ring lactone 76. The regiocheraistry of this reaction is different from that of above-mentioned diphenyl-substituted methylenecyclopropanes 66 and 67[61], This allylic lactone 76 is another source of trimethylenemethane when it is treated with Pd(0) catalyst coordinated by dppe in refluxing toluene to generate 77, and its reaction with aldehydes or ketones affords the 3-methylenetetrahy-drofuran derivative 78 as expected for this intermediate. Also, the lactone 76 reacts with a, /3-unsaturated carbonyl compounds. The reaction of coumarin (79) with 76 to give the chroman-2-one derivative 80 is an example[62]. 

Note 9) in 500 ml. of dry tetrahydrofuran i.q added to the gtirred basic mixture heated to 65° over a period of approximately 8 hours a light nitrogen stream is used to carry the methylenecyclopropane into the cold trap. After the addition is complete, the reaction mixture is stirred and heated to 65° for 3 more hours (Note 10). The trap flask contains 58 g. (43%) of methylenecyclopropane (Note 11). 

Caution The. yield isolated from this reaction depends on the efficiency of this condenser the epoxidation is exothermic and methylenecyclopropane is volatile. 

Similarly, partially fluorinated and perfluorinated methylenecyclopropanes [57, 52], cyclopropenes [55, 84, 55], cyclobutenes [75, 56], and bicychc alkenes [57, 55, 59, 90] apparently denve dienophilic reactivity from relief of their ground-state strain during reaction Thus 2,2-difluoromethylenecyclopropane and perfluoromethylenecyclopropane undergo exclusive [244] cycloadditions [57, 52] (equations 72 and 73), whereas (difluoromethylene)cyclopropane undergoes only [24-2] cycloadditions [57]... 

Reaction of the cyclopropyl-substituted pivalate (25) with dimethyl benzylidenema-lonate in the presence of a palladium catalyst gave a mixture of alkylidenecyclo-propane (26) and vinylcyclopropane (27). The ratio of these two adducts is found to be quite sensitive to the choice of ligand and solvent. While triisopropyl phosphite favors the formation of the methylenecyclopropane (26), this selectivity is completely reversed with the use of the bidentate phosphite ligand dptp (12). Interestingly there was no evidence for any products that would have derived from the ring opening of the cyclopropyl-TMM intermediate (Scheme 2.8) [18]. 

Binger, P., and Biich, H. M. Cyclopropenes and Methylenecyclopropanes as Multifunctional Reagents in Transition Metal Catalyzed Reactions. 135, 77-151 (1986). 

A positive feature of the reaction is that nitrile oxides are more regioselective, in cycloadditions to methylenecyclopropanes, compared to nitrones. Only traces (up to 5%) of the 4-spirocyclopropane regioisomers are generally observed with methylenecyclopropanes unsubstituted on the exocyclic double bond. The yields are only moderate, but higher with more stable nitrile oxides (Table 27, entries 5, 6, 10-12). 

Due to their tendency to dimerize in different thermal conditions, the formal [2 + 2] cycloaddition reaction of methylenecyclopropane derivatives and their... 

Albeit the transition metal catalysed reactions of methylenecyclopropane derivatives have already been thoroughly reviewed [2], it should be noted here that the cyclodimerization of these compounds can also be achieved by catalysis with Ni or Co complexes. The regioselectivity of the process is surprising and opposed to that of the thermal reaction, giving dispiro[2.1.2.1]octane derivatives (Scheme 69) [2],... 

The reactivity of methylenecyclopropanes with olefins, as exemplified by the following examples, is also governed by subtle structural factors, which are able to steer the outcome of the reaction towards different products arising from alternative mechanistic pathways. 

Two other [2 + 2] cycloadditions on methylenecyclopropane have been carried out with particular alkenes. The first one is the reaction with the capto-datively substituted olefin 496a, which affords the spirohexane cycloadduct 497a in modest yields (Table 39, entry 1) [126]. The low yield is partially... 

The last [2 + 2] cycloaddition performed onto methylenecyclopropane itself consists of the use of ketene derivatives, particularly of dimethylketene 508 (Table 40, entry 1) [133]. The result is an almost equimolar mixture of the two possible regioisomers 511, albeit no yield has been reported. Anyway, the particular reactivity of methylenecyclopropane was confirmed, since it was found to be around 15 times more reactive than isobutene [133]. The scarce regioselectivity of this cycloaddition was confirmed by the reactions of the same ketene 508 with 2,2-disubstituted methylenecyclopropanes (entries 2 and 3) [134], BCP has also been shown to be reactive towards chloro-substituted ketenes 509 and 510, affording the expected cycloadducts 514 and 515 in mild conditions (entries 4 and 5) [13b],... 

Some other reviews may also help the reader s understanding [2]. One useful reaction, which is not described here but which was already reviewed in the last volume of this series [60,150], is the transition metal-catalyzed [3 + 2]cycload-dition of methylenecyclopropanes. 

An alternative approach to [3 + 2 + 2]-cycloadditions has been reported by Saito and co-workers and involves cleavage of a methylenecyclopropane to produce, after capture with two alkynes, the cycloheptadiene products shown in Scheme 54.144 In a mechanistically distinct [3 + 2 + 2]-reaction, Murakami and Miura report a route to a cycloheptadienone involving the capture of two alkynes initiated by a Suzuki coupling to 2-cyanophenylboronic acid (Equation (32)).145... 

Reaction of bis(pinacolato)diboron to methylenecyclopropanes proceeds with cleavage of the proximal G-C bond of the cyclopropyl ring, giving 2,4-diboryl-l-alkenes (Equation (14)).74... 

Reaction of diaryl diselenides with methylenecyclopropanes in the presence of PhI(OAc)2 (2.2equiv.) results in ring expansion to afford 1,2-diselenylcyclobutenes (Scheme 41).206... 

Vinylbuta-1,3-diene produces the 1,2- and 3,4-mono-insertion adducts with dichlorocarbene in a 4 1 ratio [37]. A similar preference in reactivity is observed with 3-methylene-cyclohexenes [90]. 1,2-Dienes react with two equivalents of dichlorocarbene to form spiropentanes [21, 90] (Scheme 7.6). Spiropentanes (50-95%) are also obtained from methylenecyclopropanes [36,106] and by the reaction of electron-deficient alkenes with an excess of chloroform [31] (see Scheme 7.12)... 

Pentadiene 36 and isoprene (37) gave with 34a exclusively the regioisomers 39 and 40, respectively. Bicyclic methylenecyclopropanes 34a and 34b gave stereospecifically the isomers 38a and 38b deriving from the attack on the convex face of the methylenenorcarane 34a (or 34b). The reaction yields were generally good, but obtained with an excess of the diene. Only 34c gave 38c in 85% yield in the presence of only one molar equivalent of diene 35 [14]. 

The reaction of methylenecyclopropane with azides is the earliest 1,3-dipolar cycloaddition reported so far on this system [53,54]. 

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